Nano genome altas (NGA) of body wide organ responses

Wu, Bowen; Yu, Li; Nie, Nanfang; Chen, An; Liu, Yixiao; Chen, Yishan; Gong, Lin; Li, Qikai; Giusto, Elena; Bunpetch, Varitsara; Zhang, Dandan; Ouyang, Hongwei; Zou, Xiaohui

doi:10.1016/j.biomaterials.2019.03.019

Cited by 16 publications

(15 citation statements)

References 47 publications

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“…Novel delivery systems such as microparticles and hydrogels were developed for the delivery of mRNA and therapeutic protein, which effectively decreased the degradation rates of mRNA/protein and improved transfection/delivery efficiency [57][58][59]. However, the current delivery systems are difficult to achieve clinical translation due to the biodegradability of the materials and unexpected adverse inflammatory/immunological reactions [60,61]. Yu et al have demonstrated that using ADSCs [22] or fibroblasts [18] as cell-carriers for modRNA delivery, can effectively prevent the degradation of modRNA transcripts and highly express target protein without triggering any additional adverse side effects.…”

Section: Discussionmentioning

confidence: 99%

Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Peng

et al. 2022

Stem Cell Res Ther

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Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.

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Section: Discussionmentioning

confidence: 99%

Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Peng

et al. 2022

Stem Cell Res Ther

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“…41 The limitation of BRB-seq is the inability to capture low-abundance genes and address RNA splicing and fusion gene research questions. Considering these advantages and disadvantages, BRB-seq is suitable for research with high-abundance genes in large sets of samples, such as organ-specific feature discovery 42 and disease classification. OA is a heterogeneous disease with distinct pathogenic processes.…”

Section: Discussionmentioning

confidence: 99%

“…This study was approved by the local clinical ethics committees of Zhejiang University School of Medicine and the affiliated hospital of Wenzhou Medical University (2017KYLL11). RNA extraction and RNA-seq library preparation of the cartilage, synovium and subchondral bone samples were performed using the BRB-seq 13,42 protocol (details in the Supplementary Methods).…”

Section: Methodsmentioning

confidence: 99%

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

et al. 2020

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The limited molecular classifications and disease signatures of osteoarthritis (OA) impede the development of prediagnosis and targeted therapeutics for OA patients. To classify and understand the subtypes of OA, we collected three types of tissue including cartilage, subchondral bone, and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients. By applying unsupervised clustering analysis to the cartilage transcriptome, OA patients were classified into four subtypes with distinct molecular signatures: a glycosaminoglycan metabolic disorder subtype (C1), a collagen metabolic disorder subtype (C2), an activated sensory neuron subtype (C3), and an inflammation subtype (C4). Through ligand-receptor crosstalk analysis of the three knee tissue types, we linked molecular functions with the clinical symptoms of different OA subtypes. For example, the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4, which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients. Based on the marker genes of the four OA subtypes identified in this study, we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification. The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients, which may allow for precise diagnosis and treatment of OA.

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“…Multi-omics analysis can facilitate our understanding of bio-nano interactions [ 16 ]. With the development of next-generation sequencing technologies, we can concurrently characterize the transcriptome of tissues and organs in the whole body [ [17] , [18] , [19] ]. Furthermore, single-cell mass cytometry (CyTOF), which measures over 40 cellular parameters, can dissect phenotypic and functional alterations at the single-cell resolution [ [20] , [21] , [22] , [23] ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, combining Nano Genome Atlas (NGA) of multi-tissues [ 19 ] and CyTOF, we analyzed the systemic responses of USNCs at the organism level and evaluated the safety or toxicity differences comparing with HANPs, which are the Food and Drug Administration (FDA)-approved CaP NPs [ 24 ] ( Fig. 1 a).…”

Section: Introductionmentioning

confidence: 99%

Systemic and single cell level responses to 1 nm size biomaterials demonstrate distinct biological effects revealed by multi-omics atlas

Zhang

Lei

Yan

et al. 2022

Bioactive Materials

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Nano genome altas (NGA) of body wide organ responses

Cited by 16 publications

References 47 publications

Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

Systemic and single cell level responses to 1 nm size biomaterials demonstrate distinct biological effects revealed by multi-omics atlas

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